Abstract
Site-directed antibodies which modulate conformation of β-amyloid peptide became the theoretical basis of the immunological approach for treatment of Alzheimers disease (AD). Indeed, antibodies towards the EFRH sequence, located between amino acids 3-6 of the N-terminal region of Alzheimers AβP, found to be a key position in protein conformation modulation, suppress formation of β-amyloid and dissolve already formed fibrillar amyloid. The performance of anti-β-amyloid antibodies in transgenic mice models of AD showed they are delivered to the central nervous system (CNS), preventing and dissolving β-amyloid plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Naturally occurring anti-AβP antibodies have been found in human CSF and in the plasma of healthy individuals, but were significantly lower in AD patients, suggesting that AD may be an immunodeficient disorder. Active and / or passive immunization against β-amyloid peptide has been proposed as a method for preventing and / or treating Alzheimers disease. Experimental active immunization with Aβ 1-42 in humans was stopped in phase II clinical trials due to unexpected neuroinflammatory manifestations. Antibodies generated with this first-generation vaccine might not have the desired therapeutic properties to target the ‘;correct’; mechanism, however, new clinical approaches are now under consideration. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.
Keywords: alzheimer disease, monoclonal antibodies, abp, immunotherapy, n-terminal region, amyloid plaque, immunodeficiency, neuroinflammation
Current Alzheimer Research
Title: Alzheimers Disease and Immunotherapy
Volume: 1 Issue: 3
Author(s): Beka Solomon
Affiliation:
Keywords: alzheimer disease, monoclonal antibodies, abp, immunotherapy, n-terminal region, amyloid plaque, immunodeficiency, neuroinflammation
Abstract: Site-directed antibodies which modulate conformation of β-amyloid peptide became the theoretical basis of the immunological approach for treatment of Alzheimers disease (AD). Indeed, antibodies towards the EFRH sequence, located between amino acids 3-6 of the N-terminal region of Alzheimers AβP, found to be a key position in protein conformation modulation, suppress formation of β-amyloid and dissolve already formed fibrillar amyloid. The performance of anti-β-amyloid antibodies in transgenic mice models of AD showed they are delivered to the central nervous system (CNS), preventing and dissolving β-amyloid plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Naturally occurring anti-AβP antibodies have been found in human CSF and in the plasma of healthy individuals, but were significantly lower in AD patients, suggesting that AD may be an immunodeficient disorder. Active and / or passive immunization against β-amyloid peptide has been proposed as a method for preventing and / or treating Alzheimers disease. Experimental active immunization with Aβ 1-42 in humans was stopped in phase II clinical trials due to unexpected neuroinflammatory manifestations. Antibodies generated with this first-generation vaccine might not have the desired therapeutic properties to target the ‘;correct’; mechanism, however, new clinical approaches are now under consideration. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.
Export Options
About this article
Cite this article as:
Solomon Beka, Alzheimers Disease and Immunotherapy, Current Alzheimer Research 2004; 1 (3) . https://dx.doi.org/10.2174/1567205043332126
DOI https://dx.doi.org/10.2174/1567205043332126 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Foreword
Neuroscience and Biomedical Engineering (Discontinued) Opinion Paper: A Cognitive-cultural Segregation and the Three Stages of Aging
Current Aging Science Neuronal Ceroid Lipofuscinosis: The Increasing Spectrum of an Old Disease
Current Molecular Medicine Meet Our Editorial Board Member
Current Alzheimer Research Targeting Monoamine Oxidases with Multipotent Ligands: An Emerging Strategy in the Search of New Drugs Against Neurodegenerative Diseases
Current Medicinal Chemistry The Effects of Psychological Stress on Depression
Current Neuropharmacology Preface
Current Genomics Lipids as Key Players in Alzheimer Disease - Alterations in Metabolism and Genetics
Current Alzheimer Research Oxidative Stress and Amyloid Beta Toxicity in Alzheimer’s Disease: Intervention in a Complex Relationship by Antioxidants
Current Medicinal Chemistry Polyphenols and Neuroprotection against Ischemia and Neurodegeneration
Mini-Reviews in Medicinal Chemistry Hippocampal Mean Diffusivity for the Diagnosis of Dementia and Mild Cognitive Impairment in Primary Care
Current Alzheimer Research A Novel Nanoformulation of Ellagic Acid is Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer’s Disease
Current Drug Metabolism Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications
Current Pharmaceutical Design Vascular Oxidative Stress and Mitochondrial Failure in the Pathobiology of Alzheimer’s Disease: A New Approach to Therapy
CNS & Neurological Disorders - Drug Targets The Therapeutical Potential of Alpha-Synuclein Antiaggregatory Agents for Dementia with Lewy Bodies
Current Medicinal Chemistry The ATP-Binding Cassette Transporter-2 (ABCA2) Overexpression Modulates Sphingosine Levels and Transcription of the Amyloid Precursor Protein (APP) Gene
Current Alzheimer Research Gliogenesis and Glial Pathology in Depression
CNS & Neurological Disorders - Drug Targets Disturbed Sleep Patterns in Elders with Mild Cognitive Impairment: The Role of Memory Decline and ApoE ε 4 Genotype
Current Alzheimer Research Three Decades of P-gp Inhibitors: Skimming Through Several Generations and Scaffolds
Current Medicinal Chemistry Immunotherapy for Conformational Diseases
Current Pharmaceutical Design